"Psychic Detective Yakumo" centers on Saitou Yakumo, a university student with a unique ability: his left eye is red and allows him to see and communicate with spirits. Despite his reluctance to engage with the supernatural, Yakumo is drawn into solving mysterious cases involving ghosts, curses, and unresolved human emotions. His ability often places him in dangerous situations, forcing him to confront both the living and the dead.

The narrative begins when Haruka Ozawa, a fellow student, seeks Yakumo's help to investigate the strange behavior of her friend, who appears to be possessed. This encounter marks the start of their partnership, as Haruka becomes a recurring figure in Yakumo's investigations. Together, they tackle a series of supernatural cases, each tied to lingering spirits with unfinished business. These cases often reveal deeper human tragedies, such as betrayal, loss, and unfulfilled desires, which Yakumo must navigate to bring closure to both the spirits and the living.

Yakumo's character is defined by his stoic and pragmatic demeanor, shaped by a troubled past involving his family and his ability. His mother, a medium, was driven to madness by her powers, and his father, a detective, died under mysterious circumstances. These events fuel Yakumo's internal conflict and his reluctance to fully embrace his gift. Haruka, in contrast, is optimistic and empathetic, often serving as a moral compass and emotional anchor for Yakumo. Her presence helps humanize the often grim and eerie investigations.

The series also introduces Detective Gotou, a police officer who frequently collaborates with Yakumo. Gotou provides a grounded perspective, balancing Yakumo's supernatural insights with practical investigative methods. Other recurring characters include Yakumo's adoptive sister, who shares his psychic abilities, and various antagonists whose actions intertwine with the central mysteries.

The plot weaves together episodic cases with an overarching storyline involving a shadowy organization experimenting with spiritual powers. This organization's activities are linked to Yakumo's past and his father's death, adding layers of intrigue and personal stakes to the narrative. As the series progresses, Yakumo uncovers secrets about his family, his abilities, and the true nature of the spirits he encounters.

"Psychic Detective Yakumo" blends supernatural mystery with psychological depth, exploring themes of grief, justice, and the consequences of human actions. The episodic structure allows for self-contained stories while gradually building a larger narrative that ties together the characters' personal journeys and the mysteries they unravel.